In silico multi-epitope-based vaccine design for Mycobacterium avium complex (MAC) species

Leah Kashiri^1*Wonderful Tatenda Choga^2*Tinashe Musasa¹Pasipanodya Nziramasanga¹Rutendo B Gutsire³Lynn S Zijenah³Norman Mukarati⁴Simani Gaseitsiwe²Sikhulile Moyo²Nyasha Chin'ombe¹

• ¹Department of Laboratory Diagnostic and Investigative Sciences, Medical Microbiology Unit, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe
• ²Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana
• ³Department of Laboratory Diagnostic and Investigative Sciences, Immunology Unit, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe
• ⁴Department of Veterinary Clinical Sciences, Faculty of Veterinary Sciences, University of Zimbabwe, Harare, Zimbabwe

Mycobacterium avium complex (MAC) is a group of increasingly reported opportunistic pathogens that are clinically significant causing morbidity and mortality especially among immunocompromised individuals. From a genomic survey project using non-tuberculosis mycobacterium (NTM) samples in Zimbabwe, we generated complete M. colombiense (MCOL), M. avium (MAV), and M. intracellulare (MINT) genomes. Despite the burden, currently there are no approved vaccines that target multiple MAC species. Hence, we sought to design in silico, a candidate multi-epitope vaccine (MEV) that can be used against multiple MAC species. In silico vaccine design offers a rapid, cost-effective, and precise approach for identifying immunogenic epitopes and constructing multi-epitope vaccines with enhanced safety and efficacy. Using both Zimbabwean and global reference sequences, we predicted high-binding T-helper lymphocyte (THL) epitopes from the conserved immunodominant proteins including 85A, 85B and 85C from MCOL, MAV and MINT. The nine proteins yielded 82 THL epitopes, thus restricted to 13 major histocompatibility complex class II (MHC class II) alleles (DRB*) with high population coverage in the Zimbabwean and African population. After performing clustering analysis, 11 consensus peptides were formed from 26 unique epitopes, of which majority (65.4%) were from 85B. We evaluated the physiochemical properties, immunogenicity, antigenicity, and stability of the final MEV construct.Our results collectively suggest that the construct possesses strong potential potency. Additionally, the immune simulations predicted significantly high levels of IgG, T-helper, T-cytotoxic cells, INF-γ, and IL-2 upon receiving the MEV. In this study, we developed a broad and potentially effective MEV that can be used to target multiple MAC species in different populations.